Next generation sequencing technologies for a successful diagnosis in a cold case of Leigh syndrome

Paolo Aretini, Chiara Maria Mazzanti, Marco La Ferla, Sara Franceschi, Francesca Lessi, Veronica De Gregorio, Claudia Nesti, Angelo Valetto, Veronica Bertini, Benedetta Toschi, Roberta Battini, Maria Adelaide Caligo

Research output: Contribution to journalArticlepeer-review


Background: Leigh Syndrome (LS, OMIM 256000) is an early-onset, progressive neurodegenerative disorder characterized by broad clinical and genetic heterogeneity; it is the most frequent disorder of mitochondrial energy production in children. LS inheritance is complex because patients may present mutations in mitochondrial DNA (mtDNA) or in nuclear genes, which predominantly encode proteins involved in respiratory chain structure and assembly or in coenzyme Q10 biogenesis. However, during the last 15years, the discovery of several genetic mutations and improved knowledge of the natural history of LS has significantly increased our understanding of this mitochondrial disorder. Case presentation: Here we describe a 19-year-old male with clinical and neuroimaging LS diagnosed at 3years of age. Genetic analyses of the whole mtDNA for maternally inherited LS (MILS) and neuropathy ataxia retinitis pigmentosa (NARP) syndrome failed to reveal any pathogenic mutations. Conclusions: Recently, a missense mutation in ECHS1 and a ~35kb deletion in 10q26.3 involving the region including the gene were identified by WES (whole exome sequencing), uncovering the genetic diagnosis clinically hypothesized for 15years. We also report the long-term follow-up of this patient, showing a comparison with classical LS or other Leigh-like pictures.

Original languageEnglish
Article number99
JournalBMC Neurology
Issue number1
Publication statusPublished - Jul 20 2018


  • ECHS1 gene
  • Exome analysis
  • Leigh disease

ASJC Scopus subject areas

  • Clinical Neurology


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